IO Biotech’s vaccines activate T cells to modify the tumor microenvironment, targeting both cancer and immune-suppressive cells

From “Super Skeptical” Beginnings, a New Immune-Modulatory Vaccine Awaits Phase 3 Results

Data exploring a new type of tumor-fighting vaccine, presented last week at the American Association for Cancer Research (AACR), hint at game-changing news that could come by the end of the year.

IO Biotech, a Copenhagen-based developer of first-in-class immune modulating cancer vaccines, shared a pair of abstracts that shed light on how these dual-acting therapies work and showed their potential in multiple solid tumor cancers. Unlike older therapeutic vaccines, including some customized agents, these off-the-shelf vaccines activate T cells that upend the tumor microenvironment (TME), fighting cancer in 2 ways: they kill tumors cells and set loose effector T cells to create an anti-tumor, proinflammatory TME.

It’s an approach that IO Biotech cofounder and scientific adviser, Mads Hald Andersen, DMSc, PhD, said has overcome doubters, with IO Biotech recently listed as one of the world’s most innovative companies^.

IO Biotech’s technology, called T-win, works by delivering peptide epitopes to interact with antigens and launch the dual action. The lead agent pairs IO102, targeting indoleamine 2,3-dioxygenase (IDO), with IO103, targeting PD-L1.

The combination, also known as imsapepimutand etimupepimut adjuvanted and trademarked Cylembio, has received FDA Breakthrough Therapy designation. A phase 3 trial involving 407 patients, combining IO102/IO103 and pembrolizumab (Keytruda) in metastatic melanoma, will read out in the third quarter of 2025 (NCT05155254). The company expects to file a Biologics License Application with FDA by year’s end.

This comes more than 3 years after promising phase 1/2 data appeared in Nature Medicine; in that study (NCT03047928), 30 patients with advanced melanoma received a combination of IO102/IO103 and nivolumab (Opdivo).

The study, first presented virtually at the 2020 Congress of the European Society of Medical Oncology, met its primary end point of feasibility and safety and showed the combination’s toxicity profile “was comparable to that of nivolumab monotherapy.” The objective response rate (ORR) was 80% (CI, 62.7-90.5), with 43% of patients achieving a complete response (CI, 27.4-60.8).

Median progression-free survival (PFS) was 26 months (CI, 15.4-69 months) “and was not reached for responding patients.” Overall survival at 12 months was 81.6% (CI, 61.6-92). Investigators compared these results with data from a matched historical group with advanced melanoma treated with anti-PD-1 therapy—the matched group’s median PFS was 8.3 months.

What’s more, investigators were able to show that “the IDO- and PD-L1-specific T cells’ mode of action (MOA) is not limited to targeting only cancer cells. We were able to show that vaccine-specific T cell clones also reacted against PD-L1- and IDO-expressing autologous immune cells.”